The herpesviruses are the largest and most complex viruses known to be associated either directly or indirectly with various lymphomas and carcinomas in animals and man. The five human herpesviruses, herpes simplex type 1 and 2, cytomegalovirus, Epstein-Barr virus and varicella-zoster virus are harbored for long periods as latent infections in most adults and may all be capable of stably transforming normal cells in culture to tumorigenic cells. The objectives of this research project are to prepare fine structure maps of the DNA genomes of all five viruses, with a particular view towards: (a) locating and identifying functions associated with morphological transformation; (b) some insight into the biological significance of the complex patterns of inverted, duplicated and tandemly repetitious sequences observed in their DNA molecules; and (c) comparing differences and heterogeneity in their genome organization from an evolutionary standpoint. Electron microscope, restriction enzyme, gel electrophoresis and DNA hybridization techniques used recently to study and dissect the genomes of herpes simplex virus are now being applied successfully to the much harder to grow cytomegalovirus and Epstein-Barr virus DNA molecules. At the same time our attention is being focused on several areas of the herpes simplex 1 and 2 DNAs that appear to be intimately involved in initiation of DNA synthesis, generation of tandem repeat defective DNA and induction of transformed cell focus formation when added to contact-inhibited cells.